As the initial selection process did not require a change in MIC, the MICs provide complementary information about each mutation's effect, and we did not expect all beneficial (or deleterious) disruptions to cause an increase (or decrease) in MIC.
Disruptions of phoP or rob, which encode transcriptional activators of the acrAB operon [70], [71], are also deleterious, while disruption of acrR, which encodes a transcriptional repressor of the acrAB operon [72], is beneficial.
Disruption of random genes tended to be less deleterious than the disruption of hub genes (figure 1).
These processes can have both beneficial effects, creating ecologically attractive conditions for human settlement, and deleterious or disruptive ones, creating barriers to movement, disruption of ecological conditions, or hazards to survival.
This difference is higher than expected by chance, indicating that the effect of environmental stress tended to be less deleterious in random disruption strains (one-tailed binomial test, P = 0.030).
Our approach was to mine the proteomes of the model organisms Drosophila melanogaster and Caenorhabditis elegans for proteins with clear sequence similarities to those in the parasite in order to identify those experimentally proven as essential, i.e., targeted gene disruption produces deleterious phenotypes (e.g. lethal, paralyzed, impaired of motility) in both model organisms.
In this study, we have used high-throughput Illumina sequencing to characterize transposon libraries and identify genes whose disruption is deleterious for in vivo survival.
Thus deleterious effects of early disruption to cortical neuronal migration appear to include robust and widespread consequences for reorganization of neural circuitry, with apparent effects on memory systems.
Such therapy could be beneficial by removing activated cells that have deleterious effects, such as disruption of endothelial integrity and impairment of microcirculation by overproduction of proteases and oxygen radicals [ 22, 42- 44].
In addition, the greater distance of LCRs to exons is also expected to result from relaxation of selection as previous studies reported sequences near introns to be under strong selective constraints due to the presence of splicing regulatory elements and to the deleterious effects of the disruption of these elements (Pagani et al. 2005; Parmley et al. 2006; Warnecke and Hurst 2007).
